Effects of bestatin on myelopoietic stem cells in normal and cyclophosphamide-treated mice.
The effect of bestatin on hematopoietic parameters and bone marrow progenitor activity (colony-forming unit - granulocyte/macrophage: CFU-GM) was examined in normal and myelosuppressed C57BL/6 mice. CFU-GM frequency and absolute number were determined with a limiting dilution analysis of bone marrow cells in soft agar using recombinant murine colony-stimulating factor - granulocyte/macrophage. We report that bestatin increased splenic, bone marrow, and peripheral blood cellularity and the number of CFU-GM over a dose range from 2.5 mg/kg through 100 mg/kg following i.p., i.v., or oral administration. The greatest myeloid stimulation was observed following multiple injections of bestatin. Bestatin also increased the recovery from cyclophosphamide-induced myelodepression as measured by these parameters. The hematopoietic properties of bestatin following oral administration is of potential importance for clinical application.
Abe
F
F
Program Resources Inc., Preclinical Screening Lab, NCl-FCRF, Frederick, MD 21701.
Matsuda
A
A
Schneider
M
M
Talmadge
J E
JE
D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D003520:Cyclophosphamide / Q000633:toxicity*; D006098:Granulocytes / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007700:Kinetics; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D051379:Mice
D000903:Antibiotics, Antineoplastic; D003520:Cyclophosphamide; D007930:Leucine; C012211:ubenimex